DESCRIPTION: Dystonia is a syndrome of intermittent or sustained involuntary muscle contractions that frequently causes twisting and repetitive movements producing abnormal postures. These involuntary movements can affect many parts of the body (generalized) or affect more limited areas such as the focal dystonias. The pathophysiology of these syndromes remains unclear but a variety of clues suggest abnormalities of central dopaminergic pathways. We now have evidence that there is an abnormality of [18F]spiperone ([18F]SP) binding in the putamen, one of the key basal ganglia nuclei involved in motor control. [18F]SP, however, binds to both D2-like dopaminergic receptors and to S2 receptors in primate striatum. The objective of this research proposal is to determine whether patients with idiopathic focal dystonias have alterations in putaminal D2 dopaminergic receptors. Specifically, we hypothesize that patients with idiopathic focal dystonia have abnormal binding of putaminal D2-specific receptors and that receptor binding is somatotopically organized depending upon the body part involved. Additionally, we hypothesize that a genetic abnormality coding for a dopamine receptor may permit the development of these clinical manifestations. To test these hypotheses, we will measure dopamine receptor binding in vivo in patients with dystonias affecting their face (cranial dystonia) and the hand (hand cramp) as well as normals using positron emission tomography and a new dopamine D2 receptor radioligand, [18F]NMB. We will use magnetic resonance imaging to assist with precise localization of radioactive uptake in the putamen. We also will use a powerful new approach to analysis of genetic information called cladistics-based evolutionary analysis of the haplotypes of the DRD2 locus to try to identify the genetic abnormality that may predispose one to develop dystonia. These studies in addition to providing new insight into the pathophysiology of idiopathic dystonia also will help to understand and eventually treat conditions such as drug-induced involuntary movements produced by anti-psychotics as well as provide a better understanding of the function of the basal ganglia in the control of normal and abnormal movements.